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Biomedical subjects

O Richter

Publications and source records attributed to O Richter.

At least 19 recordsLinked to original sources
PubMed1994

Partitioning of chemically modified low-density lipoprotein in aqueous polymer two-phase systems.

Aqueous polyethylene glycol (PEG)-dextran two-phase systems containing 10 mM Tris.HCl (pH 7.4) were used for the partitioning of chemically modified low-density lipoprotein (LDL). Anionic modification connected with an increase in the negative surface charge of lipoproteins favours the accumulation of modified LDL in the top phase. The partition coefficient increases depending on the extent of modification. Cationic modification yields lower values for the partition coefficient. Positively charged LDL favours a bottom-phase accumulation. With weakly charged and nearly neutral particles, the Van der Waals interaction between polymer and particle preponderates over electrostatic interactions, leading to a favoured accumulation of LDL in the PEG-rich top phase. Results of measurements of the relative electrophoretic mobility and the determination of free amino groups are in agreement with the calculated values of the partition coefficient. Because the partitioning of LDL is accompanied by aggregation at the interface, experimental techniques have to be carefully standardized. Subtle differences in the surface properties of modified LDL can be detected.

Acetylation↗
PubMed1991

Partition of serum lipoproteins in a polyethylene glycol/dextran two-phase system.

Aqueous two-phase systems containing polyethylene glycol (PEG) and dextran as phase forming polymers were used for the partition of unmodified and hypochlorite modified lipoproteins. Low density lipoprotein (LDL) was separated from high density lipoprotein (HDL) by sequential ultracentrifugation from human plasma. In agreement with the higher electrophoretic mobility, high density lipoprotein shows a higher value of the partition coefficient in contrast to low density lipoprotein. An increase in the concentration of chloride ions reduces the enrichment of lipoprotein in the top phase and favours the accumulation of aggregated material at the interface. The partition coefficient strongly depends on the age of the lipoprotein sample. Differences in the value of the partition coefficient could be obtained for the lipoprotein fractions HDL-2 and HDL-3. Hypochlorite modified LDL shows higher values of the partition coefficient due to the higher negative charge of the modified lipoprotein particle.

Chemical Phenomena↗
PubMed1991

Modification of low density lipoproteins by sodium hypochlorite.

Human low density lipoproteins (LDL) were incubated with increasing amounts of sodium hypochlorite. A decrease of the number of free amino groups on the LDL surface starts only upon addition of 30-40 moles NaOCl per mole apoB, whereas all detectable SH groups are oxidized after addition of nearly 17-20 moles NaOCl. All hypochlorite-modified LDL samples have a higher electronegative surface charge compared with native LDL as revealed by agarose gel electrophoresis and partition of LDL in an aqueous polyethylene glycol/dextran two-phase system. The more NaOCl is used to alter LDL, the higher is the electrical surface charge. Changes in surface charge are found already at low NaOCl concentrations where no decrease of amino groups is detected. It is assumed that changes in surface charge are caused by the formation of monochloramines and especially at low degrees of modification by a further unknown contribution. An effect on the primary structure of apoB or peroxidation-like changes in NaOCl-altered LDL could not be found under our experimental conditions. The results are discussed with respect to such modifications under in vivo conditions by hypochlorous acid generated in stimulated phagocytosing cells.

Dextrans↗
PubMed1988

[Residues of active substances after consumption of contaminated food: status report on the evaluation of residues with examples of two drugs].

Pharmacokinetic models are presented for the computation of time courses of blood levels of drugs in man following the consumption of contaminated food. Mathematically, two linear systems of differential equations are set up for the donor organism (e.g., trout) and for the recipient, (e.g., man), where the first system generates the initial conditions for the second. Models of this kind are applied to the transfer of chloramphenicol to man via carp and trout (which had previously been administered this drug) and to the transfer of theophylline to infants via breast milk. Limiting concentration profiles are computed by constructing the most favourable and most adverse combinations of parameters with respect to drug elimination in both the donor and recipient organism.

Animals↗
PubMed1986

[Analysis of decay curves with biphasic kinetics].

Medication of trout and carps with chloramphenicol and sulfadimidine results in tissue residues which best fit by a biexponential decay curve. The analysis of residues does not reveal any systematic deviations of the data from the model. On the basis of this model half lives for the fast and slow drug elimination phases can be estimated. For the assessment of withdrawal times it is necessary to compute confidence limits for the decay curves. A withdrawal time may be defined by the intersection of recommended maximal concentrations with the upper confidence limit. This analysis does not include any metabolites. This model is also suited for monitoring purposes. It is recommended to apply the procedure to all chemicals exhibiting biexponential decay kinetics.

Animals↗
PubMed1985

Pharmacokinetic data analysis of alfentanil after multiple injections and etomidate-infusion in patients undergoing orthopedic surgery.

The pharmacokinetics of Alfentanil, a new short acting analgesic, and Etomidate, a very short acting hypnotic compound, were studied in patients undergoing orthopedic surgery. Anesthesia was induced by bolus i.v. injection of Alfentanil and Etomidate, whereas the maintenance was performed by continuous infusion of Etomidate and repetitive i.v. injections of Alfentanil. The kinetics of the analgesic can be described by a two-compartment model; the elimination half-life has a mean value of 64.8 +/- 38.5 min. No cumulation of the drug was seen in spite of multiple injections. Concerning Etomidate it is not clear whether one or two compartments are needed. The mean elimination half-life is 29.4 +/- 6.2 min. The results suggest a possible shortening of the half-life of Etomidate in the presence of Alfentanil.

Adult↗
PubMed1985

[Pharmacokinetics and pharmacodynamics of proxyphylline in asthmatic children].

In 15 asthmatic children and 3 healthy adult volunteers the pharmacokinetics and pharmacodynamics of proxyphylline under oral treatment, and the pharmacokinetics after intravenous administration were determined. The concentration-time-courses after intravenous application could best be fitted to an open 2-compartment model whereas the pharmacokinetics after oral treatment followed an open 1-compartment model. Under oral administration great inter- and intraindividual variances of the serum levels occurred. These differences which showed no age-dependency were suggested to be due to variations of the absorption velocity and the elimination half-lifes. In order to evaluate the curative efficacy of proxyphylline on lung function parameters all children had to undergo a whole body-plethysmography. No significant antiobstructive effects on the relevant baseline ventilation parameters could be observed. The protective efficacy of proxyphylline was determined in asthmatic children who developed an exercise induced asthma after a 7 minutes run. Only in 3 of 11 children a significant reduction of the enhanced airway resistance occurred. No correlation between serum levels and the protective effects was found. The present results show that there is no positive association between pharmacokinetics and pharmacodynamics of proxyphylline in asthmatic children. A safe antiobstructive therapy appears to be impossible within the dose range recommended so far.

Administration, Oral↗
PubMed1984

The relationship between pharmacodynamics and pharmacokinetics in asthmatic children receiving a sustained-release formulation of theophylline.

Pharmacodynamic response as well as serum and saliva concentrations of theophylline were monitored in 15 children under a long term theophylline treatment. Respiratory parameters, such as vital capacity and total bronchial resistance all related to bronchodilatation, were measured by use of a bodyplethysmograph. Measurements were performed before treatment and during the steady state with respect to serum levels. Due to small differences between peak and trough concentrations, no correlations between serum concentrations and respiratory parameters were found during the steady state. However, some important respiratory parameters exhibit considerable differences with respect to pretreatment values. In conclusion, one can state that during the steady state, theophylline exerts a constant influence on bronchodilatation which depends only slightly on the concentration range achieved.

Adolescent↗
PubMed1984

The kinetics of bupivacaine (Carbostesin) plasma concentrations during epidural anesthesia following intraoperative bolus injection and subsequent continuous infusion.

Plasma levels of bupivacaine were measured in 25 patients undergoing major abdominal surgery. The pharmacokinetic analysis of these data shows: (1) under a short term treatment, i.e. in the initial phase where multiple injections are given, the kinetic properties are in accordance with linear kinetic theory. The data can best be fitted to a two-compartment-model. (2) under a longterm treatment, i.e. infusion for more than 50 h, a very high accumulation occurs in contradiction to this theory. Therefore, the calculation of plasma levels from initial kinetic data is not feasible.

Adult↗
PubMed1983

Essential laboratory determinations for monitoring high-dose methotrexate treatment with citrovorum factor rescue.

The use of high-dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) has considerably improved the prognosis of some pediatric malignancies. Massive doses of methotrexate (mtx) may lead to severe or even lethal toxicity. Safe administration of this regimen requires a wide pattern of laboratory tests as well as clinical supervision. One hundred and eighteen courses of HDMTX (12 gm/m2 over 6 hours iv) with CFR administered to 12 patients were analysed for changes of routine laboratory tests 0, 6, 24, 48, and 72 hours following infusion. Hgb, WBC, and platelets on average showed no change during the 72 hours follow-up period. Serum SGOT and SGPT were elevated with a maximum 24 hours following infusion and slowly returned to normal. The increase of serum LDH values were less marked and reached a maximum at 48 hours; changes of serum y-GT values were not significant. Evaluation of the elimination of mtx from serum in each individual patient throughout 14 sequential mtx courses gave no evidence of a prolonged serum half life due to impaired renal mtx clearance. There was also no evidence of enzyme induction in the liver resulting in a shortened serum half-life. Changes of serum enzymes also were not increasing throughout treatment. Careful monitoring of serum mtx levels is mandatory when HDMTX with CFR treatment is administered. Elevation of blood urea nitrogen and creatinine levels within 24 hours following mtx treatment identify the patient at risk for slow mtx elimination and severe toxicity requiring salvage by adequate doses of citrovorum factor.

Adolescent↗
PubMed1983

Pharmacokinetics of dexamethasone in children.

A pharmacokinetic data analysis of plasma level data for dexamethasone obtained from children with various diseases and healthy adults was performed. A total of 33 subjects participated in the study. The results show: The pharmacokinetics of dexamethasone can be described satisfactorily within the frame of classic linear pharmacokinetic theory. The variance of important pharmacokinetic parameters is large. Therefore, if a close relationship between drug levels and therapeutic and adverse effects exists, which still has to be proved, optimal individual dosage regimens have to be calculated, guided by drug-level monitoring. When treating newborns, one should be aware that high drug levels are likely to occur, possibly necessitating a dose reduction.

Adolescent↗
PubMed1983

[Developing a dose-administration schedule for drug therapy in childhood].

For the application of a target concentration strategy for the assessment of dosage regimens pharmacokinetic parameters and their variances must be known. Since pharmacokinetic parameters like the elimination constant or the volume of distribution undergo considerable changes during the perinatal period until early childhood, the application of standard dosage regimens may lead to serious under- or overtreatment. Based on kinetic data of children from the literature and own studies, it is demonstrated, how changes of the volume of distribution and of the elimination constant influence the optimal dosage regimen. The optimal dosage regimen is evaluated using a special criterion of optimality.

Age Factors↗
PubMed1983

[Pharmacokinetics of drugs from the breast-feeding mother passing into the body of the infant, using theophylline as an example].

In order to find out whether theophylline medication during the lactation period would produce hazards in the suckling infant or not, the following investigations were performed: 1. After oral application of theophylline to 12 nursing mothers the pharmacokinetics of the translactal passage was determined by simultaneous measurements in serum and milk. 2. For predicting the drug uptake by the suckling infant a pharmacokinetic model was designed allowing estimations of drug uptake by the infant on the basis of the kinetics of the translactal passage and the kinetics of the drug in the infant. The following results were obtained: 1. Theophylline passes the blood milk barrier with a certain delay. The time courses of theophylline in the milk thus were depressed when compared to those in the serum. The milk/plasma-quotient varied within a range of 0.6 to 0.89 and was less when maxima of theophylline in plasma were reached. Elimination half-lifes did not differ, but the apparent volume of distribution was greater in milk. This difference showed a good correlation to the divergent areas under the curves for milks and serum concentrations. 2. The kinetic data of the translactal passage of theophylline and the kinetic data of theophylline in infants were fitted into the kinetic model presuming constant dosage intervals as well as constant amounts and intervals of drinking. Theophylline accumulation occurred highly dependent upon the half-life in the infant. This accumulation reached therapeutic levels and even could surpass these when long half-lifes were assumed. For the estimation of drug transfer from breast feeding mothers to their infants via breastmilk, several pharmacokinetic criteria should be considered.

Breast Feeding↗
PubMed1982

Improved method for routine determination of nicotine and its main metabolites in biological fluids.

ExtrelutR extraction and glass capillary gas chromatography were applied to the routine determination of nicotine and its metabolites cotinine, nicotine-1'-N-oxide and cotinine-1-N-oxide in urine and plasma. After extraction of nicotine and cotinine both N-oxides and phendimetrazine-N-oxide (used as internal standard) were reduced to their bases by SO2 on-column and eluted by a mixture of diethyl ether and dichloromethane. The minimum detectable concentrations are 0.03 micrograms/ml for urinary nicotine and cotinine and 0.1 microgram/ml for the N-oxides. In plasma samples the corresponding values are 5 ng/ml and 15 ng/ml, respectively, with sample values as small as 2 ml. The advantage of the direct determination of all four compounds of interest in one sample reduced the amount of plasma required. The straightforward and rapid extraction and reduction procedure as well as the long-term stability of the gas chromatographic separation system make the method suitable for routine application.

Chromatography, Gas↗